Cyclooxygenase-2 activity following traumatic brain injury in the developing rat
Cyclooxygenase-2 activity following traumatic brain injury in the developing rat
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DOI：
10.1203/pdr.0b013e3180db2902
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发表时间：
2007-09-01
影响因子：
3.6
通讯作者：
Graham, Steven H.
中科院分区：
文献类型：
--
作者：
Hickey, Robert W.;Adelson, P. David;Graham, Steven H.
环氧合酶（考克斯）是甘草素合成的限速酶。考克斯-2是脑内最主要的考克斯亚型，由突触活动诱导。考克斯-2产生的胡枝子素是生理条件下一系列活性的重要调节剂。然而，在病理条件下，考克斯-2活性可产生活性氧和毒性前列腺素代谢物，可加重脑损伤。在这项研究中，我们研究了考克斯-2的发育生产和测试的能力，考克斯-2抑制剂，SC 58125，以减轻创伤性脑损伤的发育大鼠。我们发现，组成型考克斯-2浓度低（0.5倍成人浓度）在出生后的第一周，然后增加到3倍的成人水平之间的第14-60天。出生后第17天（PND）而非PND 7天的受控皮质撞击（CCI）导致考克斯-2含量额外增加3倍，并与考克斯-2产物PGE增加相关（2）。在暴露于CCI的PND 17大鼠中，用考克斯-2抑制剂SC 58125治疗减弱了PGE的升高，但没有减弱损伤体积或改善Morris水中的表现
Cyclooxygenase (COX) is the rate-limiting enzyme in the production of prostaglandins. COX-2, the predominant COX isoform in brain, is induced by synaptic activity. COX-2-generated prostaglandins are important regulators for a range of activities under physiologic conditions. However, under pathologic conditions, COX-2 activity can produce reactive oxygen species and toxic prostaglandin metabolites that can exacerbate brain injury. In this study, we examine the developmental production of COX-2 and test the ability of a COX-2 inhibitor, SC58125, to attenuate traumatic brain injury in developing rats. We show that constitutive COX-2 concentration is low (0.5-fold adult concentration) during the first postnatal week and then increases to 3-fold of adult levels between days 14-60. Controlled cortical impact (CCI) at postnatal day (PND) 17, but not PND 7, caused an additional 3-fold increase in COX-2 content and was associated with an increase in the COX-2 product PGE(2). Treatment with the COX-2 inhibitor SC58125 in PND17 rats exposed to CCI attenuated the rise in PGE, but did not attenuate lesion volume or improve performance in the Morris water